Six - Cardiovascular disease in patients with chronic kidney disease

Over the past decade there has been growing recognition of the importance of chronic kidney disease (CKD) as a risk multiplier for morbidity and mortality. Impaired renal function, as measured by diminished estimated glomerular filtration rate (eGFR), is a strong and powerful graded independent predictor of cardiovascular morbidity and mortality, and of all-cause mortality (Go, et al., Tonelli, et al.). Although one of the main clinical concerns regarding CKD patients was, at one time, the preservation of renal function to retard the progression of renal failure and development of end-stage renal disease (ESRD), the risk of death in elderly CKD patients, as shown by the USRDS (Foley, et al.), is considerably higher than the risk of developing ESRD. Among ESRD patients, trends in all-cause mortality are a mirror of cardiovascular mortality, as the latter is proportionally the single largest contributor to death in these patients. Although overall mortality is lower in patients with less severe CKD, the general principle is the same: trends in all-cause mortality reflect changes in cardiovascular mortality. Moreover, the occurrence of cardiovascular mortality is not an “instantaneous” event; it reflects the development of cardiovascular morbidity. Congestive heart failure (CHF), for example, particularly in elderly patients, is characterized by significant long-term mortality. Conditions associated with the development of CHF, notably chronic kidney disease, are therefore important contributors to the larger problem of increased mortality as well. The burden of CKD is thus that it is a multiplier not only of a variety of cardiovascular conditions, but of mortality risk in patients who develop these conditions. Logically, patients with mild renal impairment — those in the earlier stages of CKD — should be targeted for prevention and treatment of cardiovascular disease before severe CKD develops. It is now apparent, however, that CKD patients have frequently been excluded from randomized clinical trials targeting cardiovascular disease (Coca, et al.), probably retarding the general acceptance of evidence-based therapies in their treatment. In this chapter we provide an overview, by CKD stage, of the mosaic of cardiovascular disease and CKD, including detailed information on the risk of incident CHF, cerebrovascular disease, peripheral arterial disease, cardiac arrest, acute myocardial infarction, percutaneous and surgical coronary revascularization, and use of implantable cardioverter defibrillators in both Medicare patients and the younger, employed patients in the Ingenix i3 dataset. Patterns of this mosaic are not always predictable. Although underuse of cardiac diagnostic testing has been reported in CKD patients, for example, use of echocardiography, nuclear imaging, and coronary angiography in patients with CHF is not attenuated by CKD stage (see Figure 6.1). Figure 6.2 provides data on unadjusted event rates for cardiovascular disease and the use of coronary revascularization and defibrillators among Medicare and Ingenix i3 patients. In both cohorts, more advanced stages of CKD are associated with a greater burden of cardiovascular disease and more frequent procedure use. Medicare patients, however, have a greater burden of cardiovascular disease, likely reflecting the important contribution of age. The next spread illustrates temporal trends and geographic variations in cardiovascular disease and the use of cardiac procedures in CKD patients. As noted by the American Heart Association, there has been a reduction over time in cardiovascular mortality in the general U.S. population, likely reflecting improvements both in lifestyle and in the treatment of heart disease. Some of this trend is evident in CKD patients as well. The overall incident rate of CHF in CKD patients dropped from 186 events per 1,000 patient years in 1997 to 154 in 2007, a 17 percent decrease. The incident rate of cardiac arrest dropped from 36.7 to 25.9, a 29 percent reduction. And for acute myocardial infarction, the incident rate fell 15 percent, from 31.6 to to 26.9. The incident rate for CVA/TIA, in contrast, fell just 3 percent over this decade, from 104.9 to 101.4, while the rate of peripheral arterial disease increased 3 percent, from 124.5 to 128.3. Over a decade, the use of percutaneous coronary intervention has increased moderately, from 12.1 events per 1,000 patient years in 1997 to 14.5 in 2007. The reverse has occurred with surgical coronary revascularization, with the rate dropping from 9.8 to 5.2. Although the overall rate of defibrillator use is numerically low, from 2003 to 2007 the incident rate of implantation increased 19 percent, from 5.1 to 6.1 events per 1,000 patient years. In the final spread we document the graded incremental relation of mortality and CKD in patients with cardiovascular conditions, and the likelihood of receiving coronary revascularization or defibrillators. We also characterize the type of physician care provided to CKD patients with a variety of cardiovascular conditions and to those receiving coronary revascularization or defibrillators, and conclude with data on per person per month costs related to specific cardiovascular conditions or procedures and CKD stage.

While CKD is a risk multiplier for the development of incident cardiovascular disease, the hazard is certainly not uniform across cardiovascular conditions. The largest hazard occurs for the risk of developing incident congestive heart failure (CHF), and this is true for both elderly Medicare patients and the younger employed patients in the Ingenix i3 database. The characterization of risk also differs in the two cohorts. Among Medicare patients, for example, the risk of incident CHF is 5 percent lower in women than in men, while in the Ingenix i3 cohort it is 31 percent lower — likely a reflection of the different demographics of CHF in elderly versus younger women. For all cardiovascular conditions, and in both the Medicare and Ingenix i3 cohorts, advanced age is an important predictor of the likelihood of developing disease. The likelihood of receiving coronary revascularization or defibrillators, however, is markedly attenuated by advanced age. Compared to patients age 66–69, those age 85 and older have a a 69–70 percent reduced likelihood of receiving an implantable defibrillator or surgical coronary revascularization, implying that less aggressive interventions may be used in very elderly patients. In the Medicare cohort, women are 66 percent less likely to receive an implantable defibrillator, and 61 and 42 percent less likely, respectively, to receive coronary bypass surgery or percutaneous coronary intervention. In the Ingenix i3 dataset, these procedures are 54, 72, and 68 percent less likely in women than in men. Tables 6.a & 6.b; see page 147 for analytical methods. December 31, 2006, point prevalent Medicare (age 66 & older) & Ingenix i3 (age 20–64) patients; comorbidities included in the model.

Unadjusted event rates for cardiovascular diagnoses and procedures are higher among Medicare patients than in the Ingenix i3 cohort, reflecting the important contribution of age to the development of cardiovascular disease and to the use of coronary revascularization and defibrillators. Among Medicare patients, rates are greatest for congestive heart failure (CHF), at 56 events per 1,000 patient years for those without CKD and 176 for those with CKD of Stages 3–5. Rates for CVA/TIA and peripheral arterial disease (PAD) are similar in Medicare patients without CKD, at 55 and 53, respectively; for patients with Stage 3–5 CKD, in contrast, PAD is the second most frequent cardiovascular diagnosis, with a rate of 130. And the event rate for acute myocardial infarction in patients with CKD of Stages 3–5 is slightly higher than that for cardiac arrest, at 28.4 versus 27.2 events per 1,000 patient years. Figure 6.2; see page 147 for analytical methods. December 31, 2006, point prevalent Medicare (age 66 & older) & Ingenix i3 (age 20–64) patients; comorbidities included in the model.

These maps present an overview of geographic variations and temporal trends in incident rates of cardiovascular disease and the use of cardiac procedures. One important overall finding is the impression of reduction in incident rates across the U.S. for congestive heart failure (CHF), cardiac arrest, and acute myocardial infarction between 1997 and 2007 — a contrast to the stability of rates seen with CVA/TIA and peripheral arterial disease. The use of coronary revascularization procedures has also changed, with a shift towards the use of percutaneous intervention and away from surgical intervention. Although overall rates have dropped for some conditions, certain geographic variations appear to have persisted. Parts of the south, for example, continue to have relatively high rates of CHF and cardiovascular conditions. It should be noted that these rates are unadjusted, so it is likely that an important relative contribution of demographic differences, such as race, contributes to these findings. Nevertheless, these data do highlight areas of the U.S. that would appear to merit additional attention to the prevention and treatment of cardiovascular disease. Figures 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, & 6.10; see page 148 for analytical methods. December 31, 1996 & 2006, point prevalent Medicare (age 66 & older) patients with CKD. For Figure 6.10, December 31, 2002 & 2006, patients.

Here we illustrate the incremental risk of CKD stage and survival for a variety of cardiovascular conditions and select procedures. In Medicare patients with incident CHF and no CKD, the estimated overall mortality at one year is 17 percent. In patients with an unknown stage of CKD, in contrast, mortality is nearly twice as high, and it reaches approximately 25 percent in patients with CKD of Stages 3–5. From the perspective of claims data, it is noteworthy that “unknown” CKD stage is prognostically at least as bad as (and sometimes worse than) CKD of Stages 3–5. From a clinical perspective, the greatest magnitude of risk is evident in AMI patients. One-year mortality is 27 percent in those without CKD, and 46 percent in those with Stage 3–5 CKD. There is also relatively high short-term mortality related to advanced CKD stage in patients receiving implantable defibrillators — at six months, 4 percent for non-CKD patients, and 15 percent for those with CKD of Stages 3–5. Figure 6.11; see page 148 for analytical methods. December 31 , 2006, point prevalent Medicare patients age 66 & older with their first cardiovascular diagnoses & procedures in 2007.

The frequent representation of cardiologists in the care of CKD patients with cardiovascular conditions is not surprising. More noteworthy is the apparent underrepresentation of nephrologists in the care of these patients. Nephrologists are involved, for example, with the in-hospital care of just 29 percent of CKD patients with an acute myocardial infarction; this falls to nearly 18 percent in the 90 days after discharge. Of patients hospitalized for cerebrovascular disease, only 50 percent are identified as receiving care from a neurologist during the hospitalization, and 18 percent in the 90 days after discharge. Figure 6.12; see page 148 for analytical methods. December 31, 2006, point prevalent Medicare patients, age 66 & older, with their first cardiovascular diagnoses & procedures in hospital, & discharged alive in 2007; patients with their first PCI or ICD/CRT-D at an outpatient clinic are also included.

Chronic kidney disease is a risk multiplier not only for incident CVD and subsequent mortality, but for cost. PPPM costs after cardiac arrest, for example, are $6,200 for non-CKD patients, and rise to $11,500 for those with Stage 3–5 CKD, and to $13,700 for those with CKD of an unknown stage. Figure 6.13; see page 148 for analytical methods. December 31, 2006, point prevalent Medicare patients age 66 & older with their first cardiovascular diagnoses & procedures in 2007.

Suggested citation for this report
U.S. Renal Data System, USRDS 2009 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2009. Publications based upon USRDS data reported here or supplied upon request must include this citation and the following notice: The data reported here have been supplied by the United States Renal Data System (USRDS). The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy or interpretation of the U.S. government.